Outline

Fulvestrant (FUL), an estrogen receptor antagonist, is a new type of hormonal agent. FUL has been shown to be as effective as aromatase inhibitors (AI) after prior tamoxifen treatment. In preclinical models, FUL exhibits no cross-resistance versus SERMs or AI. Clinical benefit rates between 15-60% were observed by different study groups investigating the use of FUL after multiple endocrine therapy and/or chemotherapy (CHT). At the time of study initiation, FUL had been approved for the treatment of advanced breast cancer (ABC) in the USA. The approval in the EU for treatment of postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer was shortly expected. To provide the patients an early access to FUL, and to increase the knowledge about the substance, the EAP programme was initiated on 29th September 2003. 88 postmenopausal women with hormone-receptor positive ABC in median age of 62 years (34-81) were examined. All patients had at least one endocrine pretreatment and progressive disease. Patients with one or more CHT pretreatments were also allowed to participate in the study, while most of the patients had received one endocrine therapy. Bone and visceral metastases were most often present, but the overall localisation of metastases was highly mixed. 11 out of 39 tumours had a 3-fold positive HER2 status (IHC). Patients received FUL 250 mg as a monthly i.m. injection. The mean duration of treatment was 12.5 weeks. 52 patients revealed the following best response during this period: 1 CR (2%), 2 PR (4%), 31 SD (60%), and 18 PD (34%). Mean overall survival (OS) was 51.8 weeks and progression free survival 13.9 weeks. The therapy with FUL was equally effective for HER2 positive as well as HER2 negative patients. There was no significant difference for OS depending on the number of CHT pretreatments. Compliance defined as timely application of FUL within the planned interval, was 97.8%. After the end of the EAP programme, 41 patients continued with an endocrine therapy, whereas 31 patients, mostly with progression of disease, changed to CHT. The EAP study demonstrated FUL as an effective and well tolerable therapy also in patients with multiple pretreatments. Compliance and therefore the therapeutical coverage of the patients was impressively shown. There was a benefit for patients with receptor positive ABC independent of HER2 status or preceding CHT. Hence, FUL is additional therapy option for ABC.